DESCRIPTION: This is an application for an Academic Research Enhancement Award requesting two years of support for a project to examine the influence of ovarian hormones on the suppression of food intake by the cytokine interleukin 1 beta. Interleukin 1 beta (IL-1) is a cytokine that is released by monocytes and macrophages activated during the acute phase response which occurs soon after infection or injury. IL-1 is responsible for many of the local and general responses to inflammation and also induces a constellation of symptoms known as "sickness behavior" (e.g., malaise, fatigue, decreased eating and drinking, lack of interest in usual activities). When administered to rats, IL-1 causes profound alterations in behavior including a suppression of food and water intake. Previous research provides strong evidence for sex differences in immune function and its modulation by gonadal steroids. These findings indicate that, in both human and non-human animals, females are immunologically stronger than males. Consistent with these observations are the findings that behavioral responses to IL-1 fluctuate across the rat estrous cycle. The suppressive effect of IL-1 on activity has been reported to be greater in estrus than in non-estrus females. These data indicate that the effects of IL-1 are influenced by ovarian hormones and suggest that interactions between gonadal steroids and cytokines may contribute to sex differences in immune response. The goals of this study are to evaluate the ability of estradiol and progesterone to modulate the inhibitory effects of IL-1 on ingestive behavior, a behavioral system in which ovarian hormones are known to exert strong effects. Information obtained from the proposed research will not only contribute to our understanding of how cytokines and gonadal steroids influence food intake, but also will also illustrate how interactions among the endocrine, immune, and nervous systems may contribute to sex differences in the immune response. Two sets of experiments are being proposed. In the first experiment the investigator will evaluate the ability of estradiol to augment the inhibition on food and water intake produced by different doses of IP injections of IL-1. The second experiment will examine the role of progesterone in estradiol IL-1 interactions.